What is the best course of action for a 30-year-old female patient with a severe, worsening headache when laying down, localized to the right frontal area to the back of the right skull, accompanied by nausea, and unresponsive to acetaminophen (Tylenol), ibuprofen, and rimegepant (Nurtec)?

Urgent Neuroimaging Required Before Treatment

This patient requires immediate neuroimaging (CT or MRI) before initiating any migraine therapy, as the clinical presentation strongly suggests a secondary headache disorder rather than primary migraine. The combination of positional worsening (worse when lying down), unilateral location, nausea, and failure to respond to multiple first-line migraine medications raises serious concern for increased intracranial pressure or other structural pathology 1.

Red Flags Demanding Urgent Evaluation

This patient exhibits multiple concerning features that mandate neuroimaging:

• Positional headache worse when lying down is the opposite pattern of typical migraine and suggests increased intracranial pressure from mass lesion, venous sinus thrombosis, or other space-occupying pathology 1
• Failure to respond to acetaminophen, ibuprofen, AND rimegepant (Nurtec) indicates this is unlikely to be primary migraine, as these represent different therapeutic mechanisms that should provide at least partial relief in true migraine 1, 2
• Unilateral frontal-to-occipital distribution can represent vascular pathology or structural lesions 1
• The conservative approach is to consider neuroimaging in patients with headache worsened by Valsalva's maneuver or atypical features that do not meet strict migraine criteria 1

Critical Differential Diagnoses to Exclude

Before treating as migraine, the following life-threatening conditions must be ruled out:

• Venous sinus thrombosis - presents with positional headache worse when lying down, nausea, and can mimic migraine 1
• Intracranial mass or tumor - causes positional headache from increased intracranial pressure 1
• Spontaneous intracranial hypotension - though typically better when lying down, atypical presentations exist 1
• Cavernous sinus pathology - can present as unilateral frontal headache with nausea that may initially respond to triptans, masking serious underlying pathology 3

Immediate Management Algorithm

Step 1: Obtain urgent neuroimaging (CT head without contrast as initial screen, MRI brain with venography if CT negative but suspicion remains high) 1

Step 2: While awaiting imaging, provide symptomatic relief with IV therapy:

• Metoclopramide 10 mg IV for nausea and direct analgesic effects 1, 2
• Ketorolac 30 mg IV for pain (if no contraindications) 1, 2
• IV fluids for hydration 2

Step 3: If imaging is completely normal, then escalate migraine-specific therapy:

• Prochlorperazine 10 mg IV can effectively relieve both headache pain and nausea 1, 2
• Consider greater occipital nerve blockade if IV medications fail 1
• Dihydroergotamine (DHE) IV or intranasal as alternative if triptans have failed 1, 2

Why Standard Migraine Treatment Should NOT Be Started First

• The pattern of positional worsening when lying down is fundamentally inconsistent with typical migraine, which usually improves with rest in a dark, quiet room 1, 4
• Failure of rimegepant (a CGRP antagonist) suggests the headache mechanism is not primarily driven by CGRP-mediated neurogenic inflammation typical of migraine 1, 4
• Treating presumed migraine without imaging in the presence of red flags can delay diagnosis of life-threatening conditions and lead to catastrophic outcomes 1

Common Pitfall to Avoid

Do not assume treatment failure means "refractory migraine" requiring escalation of migraine-specific therapy without first excluding secondary causes. The combination of atypical positional features and multi-drug failure is a red flag pattern that demands structural evaluation before proceeding with aggressive migraine treatment 1, 3.